CAJ | 학술논문

目的探讨血红素氧合酶-1(HO-1)对大鼠胆道缺血再灌注损伤的影响及其机制.方法将128只SD大鼠随机分为盐水组、空病毒组、诱导组和抑制组.分别于术前24 h经阴茎背静脉注射生理盐水、空白腺病毒、HO-1腺病毒和siRNA腺病毒0.5 ml.腺病毒注射剂量为2×109 TU/只.于再灌注1h、24 h、7d和14 d检测肝功能、胆汁成分.光镜和电镜下观察肝脏和胆管病理改变,免疫组化观察炎性细胞对胆管的浸润.Western blot分析HO-1、多药耐药蛋白、牛磺胆酸钠共转运蛋白和胆盐输出泵蛋白含量.结果手术后诱导组肝功能明显降低,肝脏及胆管组织病理学损伤减轻,肝脏汇管区小胆管及肝门部胆管周围炎性细胞较少,肝脏HO-1、多药耐药蛋白、牛磺胆酸钠共转运蛋白及胆盐输出泵蛋白含量明显高于抑制组,而抑制组血清结合胆盐、总胆红素、胆汁盐/磷脂显著高于诱导组.结论 HO-1能有效预防胆道缺血再灌注损伤,减少炎性细胞在胆管周围聚集和炎症反应,而抑制HO-1表达使胆汁中胆盐/磷脂比升高,加重胆管炎和胆汁淤积.
목적 탐토혈홍소양합매-1(HO-1)대대서담도결혈재관주손상적영향급기궤제.방법 장128지SD대서수궤분위염수조、공병독조、유도조화억제조.분별우술전24 h경음경배정맥주사생리염수、공백선병독、HO-1선병독화siRNA선병독0.5 ml.선병독주사제량위2×109 TU/지.우재관주1h、24 h、7d화14 d검측간공능、담즙성분.광경화전경하관찰간장화담관병리개변,면역조화관찰염성세포대담관적침윤.Western blot분석HO-1、다약내약단백、우광담산납공전운단백화담염수출빙단백함량.결과 수술후유도조간공능명현강저,간장급담관조직병이학손상감경,간장회관구소담관급간문부담관주위염성세포교소,간장HO-1、다약내약단백、우광담산납공전운단백급담염수출빙단백함량명현고우억제조,이억제조혈청결합담염、총담홍소、담즙염/린지현저고우유도조.결론 HO-1능유효예방담도결혈재관주손상,감소염성세포재담관주위취집화염증반응,이억제HO-1표체사담즙중담염/린지비승고,가중담관염화담즙어적.
Objective To explore the effect and mechanism of heme oxygenase-1 (HO-1) in rat bile duct ischemia-reperfusion injury.Methods 128 SD rats were randomly divided into a saline group (Saline),empty virus group (Adv),induced group (Adv-HO-1),and inhibition group (HO-1 siR-NA).Rats were injected using 0.5ml of saline,empty adenovirus,HO-1 adenovirus,and siRNA adenovirus (2× 109 TU/rat) via the dorsal penile vein 24 h before surgery.Liver function and bile composition was analyzed at 1 h,24 h,7d,and 14 d after reperfusion.The liver's histopathological changes and infiltration of inflammatory cells to the bile duct were examined,and the expression of HO-1,multidrug resistance protein (Mrp2),sodium taurocholate cotransporting polypeptide (Ntcp),and bile salt export pump (Bsep) protein were detected.Results Liver function was significantly reduced in the induced group after surgery,and hepatocytes and bile duct injury was attenuated.In comparison to the Adv-HO-1 group,abundant inflammatory cells and irregular configuration of bile ducts were seen in liver tissues of the HO-1 siRNA group.The expression of HO-1,Mrp2,Ntcp,and Bsep were significantly higher in the induced group than the suppressed group.However,serum conjugated bile salts,total bilirubin,and bile salt/phospholipid in the suppressed group was significantly higher than that in the induced group.Conclusions HO-1 can prevent biliary ischemia-reperfusion injury and reduce the accumulation of inflammatory cells around the bile duct.The inhibition of HO-1 enhanced the bile salt/phospholipid ratio aggravating cholangitis and cholestasis.